Regulation of vascular tone and arterial blood pressure: role of chloride transport in vascular smooth muscle

Recent studies suggest that primary changes in vascular resistance can cause sustained changes in arterial blood pressure. In this review, we summarize current knowledge about Cl- homeostasis in vascular smooth muscle cells. Within vascular smooth muscle cells, Cl- is accumulated above the electrochemical equilibrium, causing Cl- efflux, membrane depolarization, and increased contractile force when Cl- channels are opened. At least two different transport mechanisms contribute to raise [Cl-] (i) in vascular smooth muscle cells, anion exchange, and cation-chloride cotransport. Recent work suggests that TMEM16A-associated Ca2+-activated Cl- currents mediate Cl- efflux in vascular smooth muscle cells leading to vasoconstriction. Additional proteins associated with Cl- flux in vascular smooth muscle are bestrophins, which modulate vasomotion, the volume-activated LRRC8, and the cystic fibrosis transmembrane conductance regulator (CFTR). Cl- transporters and Cl- channels in vascular smooth muscle cells (VSMCs) significantly contribute to the physiological regulation of vascular tone and arterial blood pressure.